Contrast-enhanced MR angiography after pancreas transplantation: normal appearance and vascular complications.
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Adult↗
Biomedical subjects
Timothy L Pruett
Publications and source records attributed to Timothy L Pruett.
Effect of the 80-hour work week on cases performed by general surgery residents.
The Accreditation Council for Graduate Medical Education (ACGME) implemented mandatory work week hours restrictions in 2003. Due to the traditionally long hours in general surgery, the effect of restrictions on surgical training and case numbers was a matter of concern. Data was compiled retrospectively from ACGME logs and operating room (OR) records at a university hospital for 2002 and 2003. Work week restrictions began in January 2003. This data was reviewed to determine resident case numbers, both in whole and by postgraduate year (PGY). Mean case numbers per resident-month in 2002 were 8.8 +/- 8.2 for PGY1s, 16.2 +/- 15.7 for PGY2s, 31.4 +/- 12.9 for PGY3s, 31.5 +/- 17.6 for PGY4s, and 31.5 +/- 17.6 for PGY5s. In 2003, they were 8.8 +/- 5.2 for PGY1s, 16.6 +/- 13.9 for PGY2s, 27.8 +/- 12.5 for PGY3s, 38.2 +/- 18.8 for PGY4s, and 26.1 +/- 9.6 for PGY5s. PGY1s, PGY2s, PGY3s, PGY4s, or all classes were not statistically different. PGY5s did have statistically fewer cases in 2003 (P = 0.03). PGY5s did have statistically fewer cases after the work-hours restriction, which likely represented shifting of postcall afternoon cases to other residents. Comparing other classes and all PGYs, case numbers were not statistically different. Operative training experience does not appear to be hindered by the 80-hour work week.
Burnout, Professional↗
Independent predictors for primary non-function after liver transplantation.
Primary non-function (PNF) after liver transplantation has been found to be the most common cause of early graft loss, which accounts for up to 36% of such failures. The cause of PNF is not known. The purpose of this study was to identify factors associated with and independently predictive of PNF after liver transplantation. Four hundreds twenty-four liver transplants performed at the Charles O. Strickler Transplant Center, University of Virginia were retrospectively reviewed. PNF was defined as the failure of an allograft after revascularization with no discernable cause, leading either to retransplantation or to patient death. Risk factors were analyzed using the Pearson chi-square test for univariate analysis and logistic regression for multivariate analysis. Factors found to be associated with PNF included: female recipient (6.4% vs. 2.6%, p=0.045), African-American donor (9.5% vs. 3.2%, p=0.043), inter-racial donor to recipient transplantation (9.5% vs. 2.8%, p=0.008), severe encephalopathy pretransplant (11.1% vs. 3.1%, p=0.034), pretransplant recipient PTT > 50 seconds (10.9% vs. 2.8%, p=0.004), portal vein reconstruction with conduit (15.0% vs. 3.5%, p=0.011), and downsizing of graft (22.9% vs. 3.8%, p=0.007). Logistic regression identified the use of donor iliac vein conduit for the portal vein reconstruction (p=0.003, odds ratio=3.15, 95% confidence interval: 1.49-6.64) and the racial difference between donor and recipient (p=0.012, odds ratio=2.31, 95% confidence interval: 1.20- 4.45) to be independent predictors of PNF. The exact cause of these findings, whether physiologic or immunologic, remains unknown. If confirmed in larger data sets, the attention to these factors may minimize the possibility of PNF in non-emergency situations.
Anastomosis, Surgical↗
E2 quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation.
It is unknown whether all hepatitis C virus (HCV) quasispecies variants found within patient serum have equal capacity to associate with the liver after transplantation; however, in vitro models of HCV infection suggest that variations in the hypervariable region 1 (HVR1) of the second envelope protein (E2) may be important in infectivity. The hypothesis of the current study is that the two hypervariable regions (HVR1 and HVR2) within E2 are important in the initial virus-liver interaction, and, therefore, certain HCV quasispecies variants will be isolated from the liver after reperfusion. In 8 patients with end-stage liver disease secondary to HCV infection, HCV envelope quasispecies were determined from intraoperative serum samples obtained before the anhepatic phase of transplantation and from liver biopsies 1.5 to 2.5 hours after the transplanted liver was perfused. Explanted (native) liver biopsies were taken as a control. Sequence analysis was performed on clones of specific HCV reverse transcriptase-polymerase chain reaction products spanning HVR1 and HVR2 of the E2 protein. HVR1 was more variable than HVR2 for all samples. Quasispecies isolated from postperfusion liver differed more from serum than did explanted liver quasispecies at HVR1 (P = 0.03) but not at HVR2 (P = 0.2). Comparison of HVR1 sequences from postperfusion liver versus serum revealed significantly less HVR1 genetic complexity and diversity (P = 0.02 and P = 0.04, respectively). Immediately after transplantation but before actual infection, liver allografts select out from the infecting serum inoculum a less heterogeneous, more closely related population of quasispecies variants.
Amino Acid Sequence↗
Impact of immunomodulatory oligodeoxynucleotides on cytokine production in the lipopolysaccharide-stimulated human whole blood model.
BACKGROUND: In studying potential immunotherapeutics for sepsis, we used a lipopolysaccharide (LPS)-stimulated whole blood model to test the immunomodulating capacity of cytosine-phospho-guanine oligodeoxynucleotides (CpG ODNs). We hypothesized that CpG ODNs would have considerable counterinflammatory effects on LPS-induced cytokine production. METHODS: We administered 4 micromol/L of CpG ODNs (2216, D19, 2006, K3, or 1668) or guanine-phospho-cytosine (GpC) ODNs (control D or control K) immediately after LPS (10 ng/mL) stimulation of heparinized human whole blood. Samples were incubated for 1, 3, 6, 12, and 24 hours. Media and LPS were used as negative and positive controls. Cell-free supernatants were obtained and evaluated for interferon gamma (IFN-gamma), interleukin (IL)-12(p40), tumor necrosis factor alpha, IL-6, IL-10, IFN-alpha, IL-8, and IL-1beta by ELISA. RESULTS: Compared to LPS alone, significantly reduced levels of IFN-gamma, IL-12(p40), tumor necrosis factor alpha, and IL-6 were associated with both CpG and GpC ODNs administration to LPS-stimulated whole blood. IL-10 levels were concomitantly increased. However, IFN-alpha generation was CpG specific as was increased IL-8 levels. Lastly, only 2216 was associated with decreased IL-1beta levels. CONCLUSIONS: CpG ODNs and GpC ODNs in the LPS-stimulated whole blood model demonstrate differential counterinflammatory effects, but only CpG ODNs were associated with proinflammatory cytokine production. With further examination, we may find that these observed immunomodulatory differences could potentially be exploited for therapeutic benefit.
Adjuvants, Immunologic↗
Effect of an intensive care unit rotating empiric antibiotic schedule on the development of hospital-acquired infections on the non-intensive care unit ward.
OBJECTIVE: We have previously shown that a rotating empirical antibiotic schedule could reduce infectious mortality in an intensive care unit (ICU). We hypothesized that this intervention would decrease infectious complications in the non-ICU ward to which these patients were transferred. DESIGN: Prospective cohort study. SETTING: An ICU and the ward to which the ICU patients were transferred at a university medical center. PATIENTS: All patients treated on the general, transplant, or trauma surgery services who developed hospital-acquired infection while on the non-ICU wards. INTERVENTIONS: A 2-yr study consisting of 1-yr non-protocol-driven antibiotic use and 1-yr quarterly rotating empirical antibiotic assignment for patients treated in the ICU from which a portion of the patients were transferred. MEASUREMENTS AND MAIN RESULTS: There were 2,088 admissions to the non-ICU wards during the nonrotation year and 2,183 during the ICU rotation year. Of these patients, 407 hospital-acquired infections were treated during the nonrotation year and 213 were treated during the ICU rotation (19.7 vs. 9.8 infections/100 admissions, p <.0001). During the ICU rotation year a decrease in the rate of resistant Gram-positive and resistant Gram-negative infections on the non-ICU wards occurred (2.5 vs. 1.6 infections/100 admissions, p =.04; 1.0 vs. 0.4 infections/100 admissions, p =.03). Subgroup analysis revealed that the decrease in resistant infections on the wards was due to a reduction in resistant Gram-positive and resistant Gram-negative infections among non-ICU ward patients admitted initially from areas other than the ICU implementing the antibiotic rotation (e.g., home, other ward, or a different ICU) (1.8 vs. 0.5 infections/100 admissions, p =.0001; 0.7 vs. 0.2 infections/100 admissions, p =.02), not due to differences for those transferred to the ward from the rotation ICU (10.4 vs. 9.7 infections/100 admissions, p = 1.0; 4.3 vs. 1.9 infections/100 admissions, p =.3). No differences in infection-related mortality were detected. CONCLUSIONS: An effective rotating empirical antibiotic schedule in an ICU is associated with a reduction in infectious morbidity (hospital-acquired and resistant hospital-acquired infection rates) on the non-ICU wards to which patients are transferred.
Anti-Bacterial Agents↗
Ethnic disparities in outcome from posttransplant infections.
Black transplant recipients have decreased graft survival and increased rejection rates compared with whites. Because increased rejection rates may lead to more immunosuppression in black recipients, ethnic differences may exist for outcomes of posttransplant infectious complications. All episodes of infection between December 1996 and October 1998 on the transplant services at the University of Virginia Health Sciences Center were prospectively evaluated. Parameters recorded included self-designated ethnicity, demographics, APACHE II scores, laboratory and microbiologic data, immunosuppression, episodes of rejection, and outcome measures. Evaluation of 303 episodes of infection demonstrated an increased mortality rate for white compared with black recipients (19% vs. 3%, P = 0.0006) despite having a similar severity of illness (APACHE II score). Among renal transplant recipients, episodes of infection occurring in black recipients (n = 46) were also associated with a decreased mortality rate versus whites (n = 89) (0% vs. 15%, P = 0.006) and shorter mean length of stay (12 +/- 2 vs. 25 +/- 4 days, P = 0.002) despite similar severity of illness and rejection rates. For posttransplant infections in liver transplant recipients, blacks (n = 23) demonstrated a trend toward decreased mortality (9% vs. 26%, P = 0.07) but equal lengths of stay despite similar APACHE II scores, rejection rates, and age. White liver transplant recipients had an increased incidence of viral infections (15% vs. 0%, P = 0.03). All other infecting organisms were similar. The unexpected finding of a significantly decreased rate of mortality associated with posttransplant infections in black recipients remains largely unexplained but may be related to subtle differences in immune response between racial or ethnic groups.
APACHE↗
Contact isolation in surgical patients: a barrier to care?
BACKGROUND: Contact isolation is commonly used to prevent transmission of resistant organisms. We hypothesized that contact isolation negatively impacts the amount of direct patient care. METHODS: For 2 hours per day over a 5-week period, a single observer recorded provider/patient contact in adjacent isolated and nonisolated patient rooms on both the surgical intensive care unit (ICU) and surgical wards of a university hospital. Number of visits, contact time, and compliance with isolation were recorded, as was illness severity as assessed by APACHE II score. RESULTS: Isolated patients were visited fewer times than nonisolated patients (5.3 vs 10.9 visits/h, P <.0001) and had less contact time overall (29 +/- 5 vs 37 +/- 3 min/h, P =.008), in the ICU (41 +/- 10 vs 47 +/- 5 min/h, P =.03), and on the floor (17 +/- 3 vs 28 +/- 4 min/h, P =.039), in spite of higher mean APACHE II scores in the isolated (10.1 +/- 1.0 vs 7.6 +/- 0.8, P =.05). Among floor patients with APACHE II scores greater than 10, patients in the isolated group had nearly 40% less contact time per hour than patients in the nonisolated group (19 +/- 4 vs 34 +/- 7 min/h, P =.05). CONCLUSIONS: Because of the significantly lower contact time observed, particularly among the most severely ill of floor patients, we propose a reexamination of the risk-benefit ratio of this infection control method.
Adult↗
Does prior transfusion worsen outcomes from infection in surgical patients?
BACKGROUND: Controversy continues to exist regarding the immunomodulatory effects of cellular blood transfusions in the fields of oncology, transplantation, and infectious diseases. Numerous studies have correlated transfusion with hospital-acquired infection, but the impact of transfusion on infection-related mortality has not been addressed. The objective of this study was to determine the effect of transfusion on outcomes among infected surgical patients. METHODS: Data on all hospital-acquired infectious episodes among surgical intensive care unit and ward patients were collected prospectively over 39 months at a single university hospital. The relationships between prior transfusion (defined as the receipt of allogeneic red blood cells or platelets during the index hospitalization but prior to the development of infection) and over 100 variables were examined using univariate and multiple logistic regression analysis, with inclusion of a propensity score for prior transfusion to attempt to account for treatment selection bias. RESULTS: During the study period, 1,228 infectious episodes occurred; 641 were associated with the transfusion of packed red blood cells or platelets. Univariate analysis revealed that patients with those infectious episodes following transfusion had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (18.3 +/- 0.3 vs. 10.9 +/- 0.3, p < 0.0001) and higher mortality (26.0% vs. 8.9%, p < 0.0001). Those patients who died received a greater number of transfusions prior to infection than those who lived (7.7 +/- 0.8 vs. 4.5 +/- 0.3, p = 0.0002). Multiple logistic regression analysis revealed that the propensity score for prior transfusion independently predicted mortality (odds ratio 9.45, 95% confidence interval 3.71-24.09, p < 0.001), but that neither the presence or absence of transfusion (OR 0.89, 95% CI 0.54-1.46, p = 0.6) nor the absolute number of units of red blood cells or platelets transfused (OR for red blood cells 1.00, 95% CI 0.98-1.02, p = 0.7; OR for platelets 0.97, 95% CI 0.90-1.05, p = 0.5) independently predicted mortality. CONCLUSIONS: The transfusion of packed red blood cells or platelets prior to infection is associated with more severe disease among surgical patients, but once corrected for treatment selection bias does not appear to worsen outcomes from infection.
Anti-Bacterial Agents↗
Impact of antibiotic-resistant Gram-negative bacilli infections on outcome in hospitalized patients.
OBJECTIVE: The impact of resistant (vs. nonresistant) Gram-negative infections on mortality remains unclear. We sought to define risk factors for and excess mortality from these infections. DESIGN: Prospective cohort study. SETTING: Inpatient surgical wards at a university hospital. PATIENTS: All patients in the general, transplant, and trauma surgery services diagnosed with Gram-negative rod (GNR) infection. MEASUREMENTS AND MAIN RESULTS: All culture-proven GNR infections (n = 924) from December 1996 to September 2000 were studied. Characteristics and outcomes were compared between GNR infections with and without antibiotic resistance. Univariate and logistic regression analysis identified factors associated with antibiotic-resistant GNR (rGNR) infection and mortality. rGNR infection (n = 203) was associated with increased Acute Physiology and Chronic Health Evaluation (APACHE) II scores (17.8 +/- 0.5), multiple comorbidities, pneumonia and catheter infection, coexistent infection with antibiotic-resistant Gram-positive cocci and fungi, and high mortality (27.1%). Only seven isolates were resistant in vitro to all available antibiotics. Logistic regression demonstrated that rGNR infection was an independent predictor of mortality (odds ratio, 2.23; 95% confidence interval, 1.35-3.67; p =.002). Analysis of rGNR infection with controls matched by organism, age, APACHE II score, and site of infection, however, revealed that antibiotic resistance was not associated with increased mortality (23.6% vs. 29.2%, p =.35). Furthermore, analysis of all Pseudomonas aeruginosa infections demonstrated no significant difference in mortality between resistant and sensitive strains (18.9% vs. 20.0%, p =.85). CONCLUSION: rGNRs are associated with prolonged hospital stay and increased mortality. Infection with rGNRs independently predicts mortality; however, this may be more closely related to selection of certain bacterial species with a high frequency of resistance rather than actual resistance to antibiotic therapy. Therefore, altering infection-control practices to limit the dissemination of certain bacterial species may be more effective than attempts to control only antibiotic-resistant isolates.
APACHE↗
Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients.
To discern whether the characteristics and outcome of invasive aspergillosis in liver transplant recipients have evolved during the past decade, 26 patients who underwent transplantation during 1990-1995 (known as "the earlier cohort") were compared with 20 patients who underwent transplantation during 1998-2001 (known as "the later cohort"). Twenty-three percent of the Aspergillus infections in the earlier cohort occurred > or =90 days after transplantation, compared with 55% of such infections in the later cohort (P=.026). The earlier cohort was significantly more likely to have disseminated infection (P=.034) and central nervous system (CNS) involvement (P=.0004) than was the later cohort. The mortality rate was significantly higher for the earlier cohort (92%) than for the later cohort (60%; P=.012). Only disseminated infection (not the year of transplantation) approached statistical significance as an independent predictor of outcome. In the current era, invasive aspergillosis occurs later in the posttransplantation period, is less likely to be associated with CNS infection, and is associated with a lower mortality rate, compared with invasive aspergillosis in the early 1990s.
Adolescent↗
Improved specificity and sensitivity when using pronase-digested lymphocytes to perform flow-cytometric crossmatch prior to renal transplantation.
Several laboratories have resorted to flow-cytometric crossmatch (FCXM) in an effort to prevent hyperacute and accelerated renal allograft rejections. The currently employed FCXM has problems with both false-positive and -negative reactions, largely as a result of irrelevant IgG binding to Fc IgG receptors. In 1980, we circumvented this problem by digesting Fc IgG receptors with pronase, and demonstrated that, with immunofluorescence microscopy (IF), detection of IgG anti-HLA antibodies was highly sensitive and specific. In 1995, we introduced the pronase technique to FCXM and showed that this enzyme did not decrease HLA expression. We present herein a prospective study at our institution to determine whether FCXM using pronase-digested (PD) lymphocytes is as sensitive and more specific than FCXM with undigested (UD) lymphocytes when compared with the highly sensitive and specific IF assay. In analyzing the 186 donor-specific pre-renal-transplant crossmatches, we found that PD FCXM was as sensitive and specific as IF and was able to detect weak IgG anti-HLA antibodies that bound to B cells. Fourteen of these patients would have been denied transplants if one were to have relied on UD FCXM. The data clearly indicate that PD FCXM can reliably be used to detect weak IgG anti-HLA antibodies before renal transplantation.
Antibodies↗
Portal vein reconstruction in right lobe living-donor liver transplantation.
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Anastomosis, Surgical↗
The allocation of livers for transplantation: a problem of Titanic consideration.
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Health Care Rationing↗
Preexposure of murine macrophages to CpG-containing oligonucleotides results in nuclear factor kappaB p50 homodimer-associated hyporesponsiveness.
BACKGROUND: DNA containing the CpG motif is associated with immunomodulation of the innate immune response. Preexposure of macrophages to CpG DNA elicits a hyporesponsiveness to subsequent lipopolysaccharide (LPS) stimulation. We tested the hypothesis that this effect is due to decreased nuclear translocation of nuclear factor kappaB (NF-kappaB). METHODS: Murine macrophage-like RAW 264.7 cells were incubated with 1.5 microg/mL CpG-containing oligonucleotides (CpG ODN) for 0.5 to 9 hours followed by restimulation with 1 microg/mL LPS for 20 minutes. Some cells were cotransfected with an NF-kappaB sensitive luciferase reporter construct and a control beta-gal plasmid. Cytoplasmic and nuclear extracts were assayed for NF-kappaB by electrophoretic mobility shift assay and supershift assays, for NF-kappaB, IkappaB and phospho-IkappaB by Western blot, for luciferase activity, and for p38, c-Jun NH(2)-terminal kinase, and extracellular signal-related kinase activity assay. RESULTS: NF-kappaB functional activity was decreased as demonstrated by luciferase activity assay in the prolonged CpG ODN pretreatment groups. Unlike endotoxin tolerance, CpG ODN preexposure increased cytoplasmic phospho-IkappaB-alpha and did not abrogate mitogen-activated protein kinase activity. CONCLUSIONS: In macrophages, exposure to CpG DNA increases expression of the inhibitory p50 NF-kappaB homodimer and decreases NF-kappaB activity without inhibition of IkappaB kinases. Mitogen-activated protein kinase activity remains intact. Understanding these interactions between different toll receptor ligands may provide insight into novel therapeutic modalities.
Adjuvants, Immunologic↗
Outcome analysis of intraabdominal infection with resistant gram-positive organisms.
BACKGROUND: Although the microbiology of intraabdominal infection has been well described, the role of resistant organisms remains unclear. To evaluate the hypothesis that intraabdominal infections from resistant gram-positive cocci (rGPC) have worse outcomes compared to those with susceptible organisms, patient characteristics and outcomes were compared between these groups. METHODS: Analysis of peritoneal infections was performed on prospectively collected data of all consecutive surgical infections from December 1996 to June 1999 at a university hospital. Intraabdominal infection was defined either by a positive peritoneal cavity culture or on clinical grounds (e.g., abscess), which prompted antimicrobial or surgical therapy. Resistant Staphylococcus and Enterococcus spp. were defined as those strains resistant to oxacillin, gentamicin, or vancomycin. RESULTS: Compared to episodes of intraabdominal infection from susceptible organisms (n = 365), infections due to rGPC (n = 52) were associated with an increased severity of illness (p < 0.0001), longer time from admission to treatment (p < 0.0001), longer duration of therapy (p = 0.008), greater proportion of nosocomial infection (p < 0.0001), increased length of stay (p < 0.0001), and an increased mortality rate (9% versus 23%; p = 0.003). However, comparison of intraabdominal infection with rGPC to a group controlled for severity of illness demonstrated a prolonged time from admission until treatment and longer duration of hospitalization but a similar mortality rate between groups (17% versus 23%; p = 0.46). CONCLUSION: Intraabdominal infection with rGPC is an indicator of poor prognosis and severe illness. Although not an independent predictor of mortality, the significantly increased duration of therapy and prolonged duration of hospitalization may have considerable economic impact.
Abdomen↗
Effect of changes in surgical practice on the rate and detection of nosocomial infections: a prospective analysis.
The practice of surgery is being performed increasingly on an outpatient basis. How these changes have influenced the nosocomial infection rate and the ability of standard, Center for Disease Control (CDC)-designed surveillance techniques to detect these infections is unknown. The goal of this study was to determine whether recent changes in surgical care have led to an increased nosocomial infection rate based on number of discharges and whether current surveillance techniques are adequate to detect these complications. Data were collected prospectively on all nosocomial infections over a 1-year period on the general surgery, trauma, and transplant units at a university hospital, as independently observed by both the study team [surgical auditors (SA)] and CDC-trained infection control practitioners (ICP). The patient study group had a high acuity of illness (for 516 episodes of infection, mean APACHE II score of 15.4, 45% intensive care unit-bound, mortality of 16%). The overall infection rate per 100 discharges was 23.8 for SA and 12.2 for ICP (P < 0.001 by chi2), higher than historical reports. SA detected significantly more surgical site infections, pneumonias, and non-Clostridium difficile-related gastrointestinal infections. These relative rates of detection, however, were similar to those described previously in prior studies using similar methodologies. The nosocomial infection rate in surgical patients, based on number of discharges, appears to be increasing, perhaps due to increased inpatient acuity of illness. Current epidemiological methods provide estimates of infection rates with effectiveness similar to that reported in previous epidemiological studies but fail to recognize many infections otherwise identified by surgeons dedicated to infection control.
Centers for Disease Control and Prevention, U.S.↗